1. Field of the Invention
The present invention relates to a process for the simple and inexpensive preparation of optically active phosphorus (P-chiral) building blocks based on (−)-menthol as the chiral auxiliary. The P-chiral building blocks can be elaborated in many ways through known as well as novel reactions, for example, the stereospecific cleavage of the P(O)CH2OH motif through oxidation.
2. Description of the Prior Art
Molecular chirality plays an important role in a variety of industrial processes. Many chiral and enantiometrically pure compounds are widely used in the preparation of pharmaceuticals, cosmetics, flavors and agricultural chemicals, to name several common uses. Manufacturers of such compounds are often challenged to produce the desired enantiomer in both high yield and purity. There are several approaches to achieve these goals, including effective, but often wasteful, separations and resolutions of the desired compound or through asymmetric catalysis via the creation of chiral centers through complex chiral auxiliaries that are difficult to prepare.
The most common P-chiral compound is PhP(O)(OMen)H. This compound was first described by Mislow in the early 1970's (Farnham, W. B.; Murray, R. K.; Mislow, K. J. Am. Chem. Soc. 1970, 92, 5808). The compound was used extensively much later on by Han and coworkers (see J. Am. Chem. Soc. 2008, 130, 12648-12655, and references cited therein). Although the latter paper claims a modified preparation, the authors do not report any yield and purify the compound twice by crystallization at −30° C. Clearly, the preparation is inconvenient, expensive, and only applicable to one diastereoisomer of PhP(O)(OMen)H.
At the present time, asymmetric catalysis has proved to be the most effective method to prepare both naturally occurring and synthetic chiral compounds in large quantities. Among the most important compounds utilized for asymmetric catalysis reactions are so-called “P-chiral” ligands. Typically, these phosphine ligands have chirality in the carbon chain (C-chiral) and the phosphorous atom is symmetrical with two identical substituents RP(R1)2. Chirality at the phosphorous (P-chiral) remains the most desirable because the phosphorous is in direct contact with the metal that is actually involved in the catalysis. More selective and efficient catalysis can be attained through this proximity. To date, only a limited number of P-chiral compounds have been reported in the literature.
Because the preparation of P-chiral compounds is truly a “Holy Grail” of organophosphorus chemistry, many relevant works could be mentioned. The following reviews are exemplary of the present state of the art:    1) Grabulosa, A.; Granell, J.; Muller, G. Coord. Chem. 2007, 251, 25-90.    2) Johansson, M. J.; Kann, N. C. Mini Rev. Org. Chem. 2004, 1, 233-247.    3) Pietrusiewicz, K. M.; Zablocka, M. Chem. Rev. 1994, 94, 1375-1411.